Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/18381
Title: Photosensitizing effects of chlorin e6 - Polyvinylpyrrolidone for fluorescence guided photodynamic therapy of cancer
Authors: WILLIAM CHIN WEI LIM
Keywords: chlorin e6, photodynamic therapy, fluorescence imaging, polyvinylpyrrolidone, cancer
Issue Date: 4-Mar-2009
Source: WILLIAM CHIN WEI LIM (2009-03-04). Photosensitizing effects of chlorin e6 - Polyvinylpyrrolidone for fluorescence guided photodynamic therapy of cancer. ScholarBank@NUS Repository.
Abstract: Photodynamic therapy and fluorescence diagnosis of cancers can realize their full clinical potential if photosensitizers could be delivered specifically to tumor tissue at optimal rates and concentrations. An improvement of photophysical and pharmacokinetic parameters of existing photosensitizers can be achieved by either chemical or non-covalent modifications of photosensitizing molecules with polymers. In particular, polyvinylpyrrolidone (PVP), a water soluble and nontoxic polymer, is widely used to modify water solubility and bioavailability of various biologically active compounds. Thus, the photosensitizer-polymer formulation of chlorin e6 ? polyvinylpyrrolidone (Ce6-PVP) was developed with the rationale of providing a new photosensitizer with a high photochemical stability, good solubility both in aqueous and in biological fluids, high affinity to the target tissue, large depth of necrosis, efficient generation of the reactive oxygen species that cause destruction of the pathologically changed tissue, low phototoxicity in normal tissue as well as to provide a method of preparation of such photosensitizer. In this thesis, photodynamic therapy consists in systemic or topical administration of Ce6-PVP that selectively accumulates in the tumor tissue of a human or an animal. Following exposure to light of 665 nm wavelength, the photosensitizer produces cytotoxic species that destroy tissues. Destruction of cells by cytotoxic species, via necrosis or apoptosis leads to destruction of the tissue. Simultaneously, the irradiation at 400 nm wavelength induces fluorescence of the photosensitizer that is a sensitive diagnostic tool suitable for detecting the regions of the body which are abnormal in terms of their structural and functional condition or where intense biological processes occur, including formation of benign and malignant neoplasms. The scope of this study includes in vitro and in vivo evaluation of Ce6-PVP formulations human tumor xenograft in murine andchick chorioallantoic membrane (CAM) tumor model. In addition, we have investigated on how the polymer PVP has affected the mechanisms of penetration of Ce6 and its binding distribution to various lipoproteins. Using CAM as a drug transport model, we have demonstrated that the presence of PVP facilitates the transport of Ce6 across a biological membrane. This formulation has also been tested in selected patients in a pilot clinical trial to determine depth of penetration, specificity and selectivity of the photosensitizer for angiosarcoma and bladder cancer. It is hope that this new association of PVP with Ce6 with enhanced penetration, selectivity and photosensitizing properties towards cancer tissue will be developed as a potential photosensitizer in photodynamic therapy and diagnostics in the area of oncology.
URI: http://scholarbank.nus.edu.sg/handle/10635/18381
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